High security is safer than everywhere else in EVE Online, but in EVE Online there is no such thing as total safety. Over the years there have been many methods developed to circumvent the protections of high-sec, developed by gankers, griefers, and scammers.
Moreover, risk in high-sec is not contained to violence. This is especially true in Jita and other market hubs, where scalawags spend the better parts of their day proving that a fool and his money are soon parted. Most importantly for many players, there is an entire suite of dirty tricks that people can use to avoid CONCORD, or even to get CONCORD to blow up otherwise peaceable players without them taking any offensive action.
Take these ten tips to heart and avoid becoming the star of the next sad "should have known better" story. A little know how can go a long way toward preventing mishaps.
Maintain A Low Profile
Bragging or arguing in local chat is probably the number one reason griefers decide to hassle people.
High-sec pirates are usually the sort that declare war on weaker corporations, hoping to extort ISK or marginally humorous whining. These people are looking for larger corporations that have a lot of activity in high-sec, but not so much in the way of a PvP contingent. Basically, they are looking for soft targets. Do not present them one. If you do not have a PvP contingent, you can react by dispersing your members, joining NPC corporations, and so forth.
A big mistake that a lot of players make is getting into arguments or pissing contests in local chat, especially if they are not of immediate concern. This goes doubly for pirates and griefers, who are often motivated more by any angst that you might put into local, than financial gain. If you say something aggravating to someone with the power to hassle you, the motivation to hassle you, and a surfeit of time and boredom, don't be surprised if they take a shot at you or your corporation.
Limit Your Risk
Never carry a cargo so valuable that someone would want to expend the effort and cost to suicide gank you. My personal rule of thumb is to not carry anything worth more than 10mil ISK in a frigate, 80mil ISK in a cruiser, 120mil ISK in a battleship, or 900mil ISK in a freighter. Avoiding having an excessively valuable cargo will dissuade many from trying to suicide gank you, and will reduce the cost-benefit margins of anybody that decides it is worth it.
Do not use autopilot if you are carrying valuable goods or are at war. Doing so while at war is the height of folly, really. I think this is pretty self-explanatory. Also, when using autopilot to plan your route (i.e. all of the time), carefully check any autopilot routes to make sure that they do not take you into low-sec or null-sec. The dots along the left side of your screen will be color coded according to what security status the systems are, which is a quick clue for non-color-blind players.
If you are a miner, another way to limit your risk is by sticking to solar systems with security classes of .8 or higher. In these systems, suicide ganking is a bit harder to do because ganking ships have less time before CONCORD destroys them. It can be the difference between two volleys with weapons or three.
Don't Take Candy From Strangers
Never take anything out of a stranger's jet can. Never join a stranger's fleet without a compelling reason. Never allow a stranger to join your fleet. Do not use a remote-repair module on a stranger. Any of these could potentially allow someone to attack you, get you killed by CONCORD, or allow someone that they have attacked recently to attack you.
Especially never do any of these things if you are in a "please gank me" ship like a Caldari navy raven or some sort of marauder, running level four missions in a popular mission hub like Motsu. That's just asking for it.
Control Your Temper
It isn't worth it. It doesn't matter what it is, it isn't worth it. People will try to get you to attack them over a can of ore, salvage, or stolen loot. Even if you somehow have the upper hand --which is unlikely, since they have chosen the time and place of provocation- it is still a bad idea to make a move.
Doing so would only play into the griefers' hands and validate that method of gameplay. A wise man once said that the best revenge is a life well lived. Ignore the hassle, change up your game plan, relocate, whatever. Just don't give the aggressor what he wants.
Do Not Trust CONCORD
Did you know that you can get killed by CONCORD if you use a remote shield or armor repair module on someone, then that person can attack someone else and both of you will get killed by CONCORD? Did you know that if you attack someone that steals from one of your wrecks, and then dock, then that person can prolong the window during which the two of you can safely fight, by shooting your wrecks that you left in space? Dirty pool, all of it, but still stuff that you need to be aware of. CONCORD should be your last line of protection, not your first.
The best counter to this level of gameplay, just at the cusp of what is legal and what is an exploit, is to assume that your enemy has a plan and is following it, rather than just reacting. As in life, it is better to act when you have a well-considered plan, rather than to react to unfortunate circumstances without consideration.
For example: say a fellow steals ore from your can, or loot from your mission. He could have friends nearby. They could be in his corporation, so that once combat began they could get involved. In which case you might notice in local chat. More dastardly, they could be logged off in that system, but ready to log on at a moment's notice. Or even worse, there could be neutral characters ready to repair shields or armor, and you would never know until it was too late.
In short, unless there are really high stakes it is very risky to engage someone, even if they seem a bit incompetent. Your best weapon here is your instincts. If you think something is awry, you are probably right. Go with your gut.
High security space is safer than the rest of EVE Online, but safety is ultimately an illusion. As long as you undock, you can be blown up. As long as you buy or sell things, you can be scammed. But if you can stay frosty and not expose yourself, you will probably be all right.